Advanced Tissue Staining System with Humidity Controller and Method

An automated system for depositing reagents on biological specimens.

In various settings, processing and testing of biological specimens is required for diagnostic purposes. Generally speaking, pathologists and other diagnosticians collect and study samples from patients, and utilize microscopic examination, and other devices to assess the samples at cellular levels. Numerous processing steps typically are involved in pathology and other diagnostic processes, including the collection of biological samples such as blood and sample, preparing the samples, preparation of microscope slides, staining samples on microscope slides, examination, re-testing or re-staining, collecting additional samples, re-examination of the samples, and ultimately the offering of diagnostic findings.

Sample (e.g., sample) staining processors or stainers can be operated with varying levels of automation to process human or animal sample specimens for histology or pathology uses. Various types of chemical reagents can be used at various stages of sample processing and various systems have been developed for delivering reagents to specimens containing slides. Examples of known reagent delivery systems include small quantity release dispensers, manual pouring into reagent vats, or via bulk containers connected with a stainer via tubing.

There are various disadvantages of known systems. For example, manually pouring into, or draining, reagent vats is susceptible to cross contamination, is time consuming and requires pouring accuracy, thereby decreasing the overall efficiency and accuracy of the sample processing system. Another disadvantage is that manually pouring and draining reagents can be sloppy, requiring clean-up of spills and consequential instrument down-time. A further disadvantage is that manually selecting and applying the correct reagent introduces significant risk of human error and increased possibility of reagent selection errors and application errors resulting in false positive or negative assay results, leading not only to a decrease in test accuracy and operational efficiency but also misdiagnosis.

In the following paragraphs, the invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this description, the embodiments and examples shown should be considered as exemplars, rather than as limitations on the present invention. Furthermore, reference to various aspects of the embodiments disclosed herein does not mean that all claimed embodiments or methods must include the referenced aspects.

A sample processor is disclosed. The sample processor representatively includes a body including an inner surface that defines a chamber including an opening in a side of the body and comprising a volume to accommodate a least one microscope slide therein. The sample processor also includes a door including a first position to cover the opening of the chamber and a second position to expose a portion of the chamber through the opening; a slide bed disposed in the chamber; and one of an internal humidity generator disposed in the chamber and an external humidity generator coupled to the chamber. The sample processor may be a stand-alone sample processor or may be combined with one or more other similar sample processors as part of a sample processing system.

1 FIG. 1 FIG. 2 FIG. 2 FIG. 112 120 120 112 125 125 125 120 120 125 120 120 120 120 120 120 112 122 125 120 122 120 135 135 125 122 120 125 125 125 shows a perspective side view of a sample processor. Sample processorincludes body. Bodyof sample processorin this representative example is rectangular and includes a top, a base and a pair of opposing sidewalls that define a length dimension (z direction) and a separate pair of opposing sidewalls that define a width dimension (x direction) with the top, the base and the two pairs of sidewalls collectively defining chamberto accommodate a single microscope slide therein. Representatively, a microscope slide may be a flat piece of glass having a thickness of one millimeter (mm) (0.04 inches) and a length of 75 mm (about 3 inches) and a width of 26 mm (about 1 inch). A length of chambermay be on the order of 80 mm to 100 mm (3.2 inches to 4 inches) and a width of chambermay be on the order of 28 millimeters to 40 millimeters (1.1 inches to 1.6 inches). It is appreciated that bodymay have other shapes besides rectangular so long as the shape can accommodate a single slide. In another representative example, bodymay have dimensions to accommodate multiple slides in chamber(e.g., two slides, three slides, four slides). Bodymay be made of a material that is chemically inert to the reagents commonly used in a staining process or a tissue processing process to prepare a tissue for staining. Representative metal material includes, but is not limited to, stainless steel, zinc alloy, aluminum alloy, silver. A silver material may be used, for example, to impart antimicrobial properties to body. Other exemplary material for bodymay include heat-transferable polymeric materials such as plastics or cellulosic (i.e., cellulose based or comprising) materials, ceramic, Teflon®, glass etc. Bodycan be formed by any process known in the art such as injection molding, machining or any other manufacturing process suitable for generating the desired features. In addition, it should be appreciated that bodycan be composed of more than one of the above discussed materials.also shows bodyof sample processorincludes openingin one side to access chamber. In the illustrated embodiment, opening is in a sidewall (e.g., a front sidewall of body). Disposed around openingof bodyas viewed is gasket or sealof a rubber or other polymer material. Gasket or sealmay serve to seal or substantially seal (e.g., hermetically seal) chamberwhen a door covers openingin body(see). Representatively, chambermay be able to be completely sealed (i.e., hermetically sealed so that no air or gas can escape chamberand fluid sealed so that no fluid can escape from chamber).shows a perspective side view of a sample processor with a door of a body of the sample processor in a closed position.

112 122 125 130 120 122 130 132 120 130 130 130 120 134 134 132 130 130 120 134 132 130 Sample processorincludes a door of, for example, a plastic or metal material (e.g., stainless steel, zinc alloy, aluminum alloy, silver) having dimensions to cover openingto chamber. Doorincludes a generally rectangular portion having length (z-direction) and width (x-direction) dimensions similar to the side of bodydefining opening. One end of door(a top end as viewed) includes clevis portionprojecting in a length direction (z-direction) from the generally rectangular portion. An opposite second end is connected to a base of bodyby a hinge so that doorcan be rotated between a horizontal (z-direction) open position and a vertical (y-direction) closed position. The movement of doorbetween an open position and a closed position may be controlled by a motor that, for example, rotates an axle disposed through the hinge so that doorrotates on the axle. Connected to a top surface of bodyis latch member. In this example, latch memberis a horizontal U-latch toggle clamp that engages with clevis portionwhen dooris in a vertical closed position and clamps doorto body. It is appreciated that latch memberand clevis portionmay be an electronic door latch mechanism and/or an electromechanical door latch mechanism that may be electrically connected to a controller including non-transitory, machine-readable instructions to control the latching as well as the opening and closing of door.

125 120 115 115 1152 1152 1152 1153 1152 1151 1151 150 1151 1152 1151 1152 1157 1151 1153 1152 1152 1158 1151 Disposed within chamberof bodyis slide bed. Slide bed, in this example, includes platenthat has rectangular shape with a planar top surface having dimensions to accommodate a microscope slide laying horizontally as viewed on platen(e.g., length (z-dimension) and width (x-dimension) equivalent or slightly greater (e.g., 1 millimeter (mm) to 2 mm greater) than a microscope slide). Surrounding one z-dimension side and a first end of platen(a left end or front end as viewed) is a y-dimension projecting lip. Disposed on platenand connected thereto is platformthat has dimensions similar to a microscope slide (e.g., 75 mm by 25 mm). Platformwill support a microscope slide thereon (microscope slide). Platformhas z- and x-dimensions less than platen. The smaller z- and x-dimensions of platformrelative to platencreates a gutter (gutter) between an edge of platformand lipprojecting from an edge of platen. One end or both ends (z-dimension ends) of platenmay also include an opening (opening) therethrough to allow drainage of reagents introduced on platform.

1 FIG. 115 1154 1152 1154 1152 1155 As shown in, a second end of slide bed(a right end as viewed) includes step portionthat is in a different plane (a higher y-dimension plane as viewed) than platen. Step portionis separated from platenby rampthat is positioned at an angle on the order of 20° to 45°.

1 FIG. 150 1151 115 150 1152 1152 1152 shows microscope slidedisposed on platformof slide bed. Microscope slidemay have a sample (e.g., a tissue sample) thereon and the microscope slide may be positioned on platenwith the sample facing away from platen(facing upward as viewed) or facing platen(facing downward as viewed).

3 FIG. 3 FIG. 3 FIG. 2 FIG. 115 115 112 115 142 140 144 142 144 115 144 144 115 115 115 144 115 115 144 115 144 115 115 115 1153 1152 1153 115 150 115 115 shows a top side perspective view of slide bedand a mechanism that controls movement of slide bedisolated from other components of sample processor. Referring to, in this example, slide bedis operable to be rotated lengthwise in one direction to, for example, remove liquid.shows shaftconnected at one end to rotary motor(stepper, brush DC or brushless servo) and including collararound a second opposite end of shaft. Collaris disposed below slide bed. Collar, in one example, has a xy cross-sectional shape of a Fibinacci spiral. A Fibinacci spiral representatively gets wider (or further from its origin) by a certain factor for every quarter turn it makes. In this configuration, collaris disposed below slide bedso that as collar rotates (e.g., clockwise), only the widest point or quadrant of the spiral shape contacts a bottom surface of slide bedand lifts slide bedat the widest point that allows collarto contact and lift slide bed. A contact point of slide bedby collarat its widest point may not be at a x-dimension midpoint of the slide bed but may be offset a small distance (e.g., 1 mm to 2 mm) to one side (e.g., a left side as viewed) so that the lifting of slide bedby collarcauses one z-dimension side of slide bedto be raised so that slide bedtilts downward to the other z-dimension side as illustrated in. The raised z-dimension side of slide bedincludes lipat the edge of platenwhile the other lowered side may not include lip. The tilting of slide bedallows for removal of excess fluid (e.g., reagent) that may be on microscope slideon slide bedor on slide beditself to drain off the lowered z-dimension side.

1 3 FIGS.- 140 120 140 160 160 152 120 122 142 140 120 142 144 125 120 142 125 125 As illustrated in, rotary motoris located outside of body. Rotary motoris connected to bracket. Bracketis seated and connected to platformwhich is connected to a side of bodyopposite the side including opening. Shaftextends from rotary motorthrough an opening in bodyso that a portion of shaftand collarare inside chamber. The opening in bodythrough which shaftis disposed may be sealed with, for example, a gasket (i.e., hermetically sealed so that no air or gas can escape chamberand fluid sealed so that no fluid can escape from chamber).

112 115 112 155 1552 1554 1556 1552 152 1552 1556 1556 160 112 162 164 169 125 160 169 1154 115 120 162 164 125 125 Sample processoralso includes a mechanism to move slide bedin a z-direction. Sample processorincludes linear actuatorthat includes rotary motor(stepper, brush DC or brushless servo) and threaded lead screwwith captive precision nut. Rotary motoris disposed below and connected to platformin this example. Rotary motoris connected to precision nutand lead screw is threaded into precision nut. A distal end of lead screw (right side as viewed) is connected to bracket. Sample processoralso includes rodand rodparallel to one another and each fixedly connected at a proximal end (left end as viewed) to bracketinside chamberand at a distal end (right side as viewed) to bracket. Bracketis positioned below and connected to stepof slide bed. The openings in bodyfor rodand rodmay be sealed with, for example, a gasket (i.e., hermetically sealed so that no air or gas can escape chamberand fluid sealed so that no fluid can escape from chamber).

1552 155 1556 1554 1554 1554 160 112 166 152 160 166 155 As a rotor of rotary motorof linear actuatorspins, the linear actuator converts the rotation of the motor into linear motion by moving rotating nuton lead screwcausing lead screwto move in a z-direction. The movement of lead screwcauses bracketto also move in a z-direction. Sample processorfurther includes a pair of rails or trackson platform. Bracketis connected to the pair of rails or tracksand can move in a z-direction on the rails and tracks in response to movement directed by linear actuator.

155 152 120 122 130 115 125 120 115 120 120 1 FIG. 4 FIG. Linear actuatoris connected to platformwhich is connected to a side of bodyopposite the side including opening. When dooris in an open position (see), linear actuator may move slide bedfrom a position within chamberof bodyto a position outside the chamber as shown in. When slide bedis outside body, a microscope slide may be placed on an empty slide bed or, if present, removed from a slide bed. One or more processing treatments may also be introduced to a sample on a slide bed when the slide bed is outside body.

112 120 125 115 125 156 157 120 120 125 125 156 125 157 125 156 125 156 125 120 158 125 158 159 120 159 1 FIG. 1 FIG. Sample processormay function as a humidor capable of manipulating and maintaining humidity to reduce reagent evaporation and sample (e.g., tissue) drying. A representative humidity level may be a relative humidity above 50 percent, such as above 60 percent to 100 percent, such as 70 percent to 100 percent, such as 80 percent to 100 percent, or such as 90 percent to 100 percent. In the example illustrated in, bodyincludes chamberthat has dimensions to accommodate a reservoir beneath slide bed. The reservoir may be filled with water to produce humidity in chamber.shows valveconnected to conduitthat extends from a point outside bodythrough a bottom wall of bodyto a point inside chamber(e.g., a few millimeters inside chamber). A fluid (e.g., water) source may be connected to valveto introduce fluid into chamber. Conduitmay also include a flow meter to monitor the amount of fluid introduced into chamber. In one example, valveand a flow meter, if present, may be electrically connected to a controller that includes non-transitory machine-readable instructions to introduce a certain volume of fluid into chamberthrough valve. Also extending from chamberthrough a base wall of bodyis conduitthat may serve as a drain to drain the fluid contents of the reservoir in chamber. Conduitis connected at a distal end to drain valveoutside body. In one example, valvemay be electrically connected to a controller that includes non-transitory machine-readable instructions to actuate the valve (open, close).

112 154 154 125 154 157 125 154 154 125 112 125 125 1 FIG. 1 FIG. Sample processorinalso includes heat element. In the example shown in, heat elementis an immersion heater installed directly into the reservoir of chamber. In another example, heat elementmay be positioned on or in conduitto heat fluid being delivered to the reservoir of chamber. Heat elementmay be an electrically powered resistive heat element. Heat elementmay be electrically connected to a controller that includes non-transitory machine-readable instructions to power and control the heat element through, for example, a thermostat. The ability to heat a fluid (e.g., water) in the reservoir allows chamberof sample processorto produce humidity at elevated temperatures by producing water vapor. An ultrasonic humidifier could also be placed in the reservoir and powered to expel reservoir droplets within chamberthat evaporate and humidify chamber.

125 112 159 158 125 Another technique to produce humidity in chamberof sample processoris to introduce air or an inert gas (ambient or heated) through the fluid reservoir to produce a humid environment. Representatively, air or an inert gas from an ambient or heated source can be connected to drain valveand the air or inert gas can be introduced into the reservoir through conduit. A further alternative is to use an ultrasonic humidifier to expel tiny water droplets into the air that evaporate into water vapor, humidifying chamber.

125 112 112 125 156 The production of humidity from a reservoir in chamberof sample processorcan result in the reduction of a volume of fluid in the reservoir. For example, water will evaporate as it produces humidity in the chamber. To monitor a fluid level in the reservoir, sample processormay include a sensor, such as a float sensor, in the chamber that sends a signal, such as to a controller, indicative of a level of fluid in the reservoir. When the fluid level drops (the volume decreases) to a predetermined point, additional fluid is added to the reservoir (e.g., non-transitory machine-readable instructions from a controller direct the introduction of a certain volume of fluid (e.g., water) into chamberthrough valve.

112 125 120 125 125 120 Sample processormay also include a humidity sensor in chamber. Representatively, a humidity sensor may be connected to a top wall of bodyinside chamberand provide an indication of a humidity level in chamber. A humidity sensor may be connected to a visual indicator like a display (e.g., a liquid crystal display) outside chamberor connected to a controller that may include non-transitory, machine-readable instructions to control humidity levels (e.g., to produce, reduce or maintain an amount of humidity in chamber).

125 112 125 125 157 125 157 125 157 Another option to produce humidity in chamberof sample processoris to produce humidity from an external source rather than from a reservoir in chamber. Steam produced in an external boiler may be supplied into chamber, such as through conduit. Air or an inert gas (ambient or heated) may be bubbled through an external reservoir (ambient or heated) to produce humid air at a desired moisture level that could be supplied into chamber, such as through conduit. Further, an ultrasonic generator could produce water droplets (ambient or heated) that could be fed to chamber, such as through conduit.

Sample processing techniques may involve processing a sample (such as a tissue sample on a microscope slide) at other than ambient pressure and/or other than ambient temperature. Representative pressure for certain sample processing operations may be 1 atmosphere (atm) (ambient) to 3 atm (14.7 pounds per square inch (psi) to 44.1 psi), such as 1 atm to 2 atm (14 psi to 29.4 psi), or such as between 1 atm and 2 atm, such as 1.7 atm (25 psi). Representative temperature for certain sample processing operations may be 20° C. (approximately ambient) to 150° C., such as between 20° C. and 150° C., such as 30° C. to 140° C., such as 40° C. to 130° C., such as 50° C. to 120° C., such as 60° C. to 110° C., such as 70° C. to 150° C., such as 100° C. to 140° C., such as 110° C. to 140° C., or such as 120° C. to 130° C.

112 125 120 130 120 120 112 170 112 172 120 125 172 120 170 172 170 172 174 175 176 174 125 174 125 175 125 125 176 112 125 176 176 172 170 176 2 FIG. 1 2 FIGS.and To increase pressure in sample processor, air or an inert gas may be introduced into chamberof bodywhen dooris in a closed position and bodyis hermetically sealed (see). Connected to bodyof sample processormay be compressor or pumpthat is a source of compressed air or inert gas. Representatively, sample processormay include fitting(e.g., a valve or valve and conduit) disposed in bodyto chamber.show fittingconnected to bodyon the top wall of the body. It is appreciated that it may be connected to another wall (e.g., a sidewall, the bottom wall). Compressor or pumpmay be connected to fittingvia a conduit, e.g., a plastic or metal conduit. Disposed in the conduit between compressor or pumpand fitting, in this example, is pressure regulator, pressure release valveand pressure gauge. Pressure regulatormay be used to regulate (e.g., set) a desired or predetermined pressure in chamber. Pressure regulatormay allow a steady or constant pressure (e.g., elevated pressure) in chamberor pulses of increased pressure. Pressure release valvemay be used to release excess pressure built-up in chamberor to return chamberto an ambient pressure. Pressure gaugemay be used to indicate to an operator of sample processora pressure level in chamber. Pressure gaugein the illustrated embodiment includes a sensor and a display. It is appreciated that pressure gaugemay not include a display at the point of connection in the conduit between fittingand compressor. Pressure gaugebe connected, for example, electrically to a monitor that displays a pressure value read by the sensor in the conduit.

125 125 120 120 120 125 130 125 Another technique to increase pressure in chamberis to modify the volume of chamber. This may be done, for example, by compressing one or more of a top, bottom or sidewall of body. For example, the upper portions of the sidewalls of bodymay have concertinaed sides to allow the sidewalls to expand and contract. The concertinaed sides allow a downward force on the top of bodyto compress the concertinaed portions of the sidewalls like an accordion to decrease a volume of chamberand, when the compression is done with doorin a closed position, to increase a pressure in chamber.

112 125 125 125 115 115 115 125 120 125 125 Sample processormay modify a temperature in chamber. One way a temperature in chambermay be increased is by heating a fluid in a reservoir as described above with respect to generating humidity levels in chamber. In addition to this technique or as an alternative, slide bedmay include a heater such as a thermocouple in contact with an underside of slide bed. Another heating technique includes one or more heaters to heat the ambient area around slide bed. Examples include resistive electrical heaters or infrared heaters positioned within chamber. A still further technique is a heat jacket wrapped around an exterior of bodyto heat chamberfrom outside the chamber. The heat source(s) may be connected to a controller allowing machine-readable, non-transitory instructions associated with the controller to control the heat source(s) and control a temperature in chamber.

Sample processing such as tissue processing to prepare a tissue sample on a microscope slide for pathological evaluation typically involves many steps. Representatively, such steps include heating to adhere a tissue sample to a microscope slide, dewaxing to remove paraffin and expose the sample, antigen retrieval to expose antigenic sites in or on the tissue sample and one or more staining operations using dyes or labels to color tissue sections and make them visible under a microscope to allow the sample to be evaluated. Representative dyes include hematoxylin, eosin, Masson's trichrome, modified GMS silver stain, periodic acid Schiff, and Perls' Prussian blue iron. Other methods of staining include, but are not limited to, immunohistochemistry or in situ hybridization to target specific proteins or DNA/RNA sequences in a sample.

Many of these steps in sample processing involve contacting the tissue sample with one or more reagents. These include bulk reagents and primary reagents. Examples of bulk reagents include, without limitation, the following: Tris Buffered Saline (TBS), Saline Sodium Citrate (SSC), distilled water, dewaxing solution, alcohol and xylene. Examples of primary reagents include without limitation, stains, such as hematoxylin and eosin, any type of antibodies, probes, nucleic acids (RNA, DNA or oligonucleotides), ligands, ligand receptors, enzymes or enzyme substrates or any other molecules suitable for a desired use. The reagents can be in a natural form, purified, concentrated, diluted or otherwise conditioned. Additional primary reagents may include signal molecules such as fluorescent dyes, enzymes, conjugates (e.g., biotin, avidin, streptavidin), metals (such as silver or gold particles), dyes, stains, radioactively tagged molecules, or any other substances such as signaling or reporter molecules.

112 125 125 125 125 121 120 121 120 125 121 1155 115 121 1155 150 150 125 121 125 150 1155 1154 1155 1157 1 FIG. Referring to tissue processor, a dispensing of reagents onto a sample on a microscope slide may take place with the microscope slide either outside of chamberor inside chamberor a combination of inside and outside chamberdepending on the reagent. Bulk reagents, for example, may representatively be dispensed onto a microscope slide inside chamber.shows openingthrough a top of body. Connected to openingmay be a conduit (not shown) to which a reagent may be connected to dispense the reagent from outside of bodyand chamber. One reagent may be connected to the conduit or multiple reagents may be connected to the conduit through, for example, a manifold. Openingis directly above rampof slide bed. Reagents introduced through openingmay contact rampand flow by gravity onto slideor under slideif the slide is positioned with a sample side down. There can also be a nozzle or nozzles inside chamberconnected to a conduit through opening. Such a nozzle or nozzles can be operable to dispense a spray or a curtain flow (wide laminar flow) of reagent inside chamber. Such nozzle or nozzles may direct a flow of a reagent onto a top surface of slide(when a microscope slide is positioned with a sample side up as viewed) or onto rampand/or step portion(when a microscope slide is positioned with a sample side down as viewed) or when purging a reagent or the conduit so that purged reagent goes from rampdirectly into gutter, such as when a microscope slide is positioned with a sample side up.

5 FIG. 1 FIG. 120 125 121 121 190 190 190 120 130 120 191 190 191 190 191 191 191 192 125 shows a perspective top side view of an underside of the top of bodyillustrating another technique for dispensing reagent(s) onto or under a microscope slide inside chamberas an alternative to openingor in addition to opening. Disposed projecting from one side of the top are a number of fluid connectors(e.g., 4-8 fluid connectors). Fluid connectorsmay be fittings or couplings that allow a fluid conduit (e.g., polymer tubing to be connected thereto). Representatively, fluid connectorsmay project from a right side of the top of bodyas viewed from(a side opposite door). An underside of the top of bodyincludes a number of conduitsdisposed lengthwise across a length of the top. Individual ones of fluid connectorsare fluidly connected to conduitsso that fluid may be delivered through fluid connectorsto conduits. Conduitsmay be a tubing material such as a metal (e.g., copper, aluminum, stainless steel). Each conduitmay have openingsalong its length to discharge a fluid from the conduit in a direction of slide bed. Each opening in a conduit may include a nozzle to control a flow direction and rate. The dispense of a reagent from each conduit may be a flow, a spray or a liquid curtain to provide optimum coverage of the sample on a microscope slide or of the entire microscope slide surface.

190 190 191 In one example, bulk reagents may individually be connected to fluid connectors. The bulk reagents may be contained in individual containers and be connected to individual ones of fluid connectorsthrough conduits running between, for example, a respective bulk reagent container and a fluid connector. A bulk reagent may be supplied to a fluid connector through the use of a pump as necessary, such as an individual in-line pump for each bulk reagent container connected to a fluid connector. Non-transitory, machine-readable instructions associated with a controller may control the metering of a reagent from a bulk reagent container such as by a timer or by an individual in-line flow meter (e.g., a flow meter in a conduit between the bulk reagent container and the fluid connector). A temperature of a reagent dispensed may be altered or controlled through pre-heating or cooling, as necessary, prior to the dispense. Representative techniques for modifying a temperature of a reagent to be dispensed include heating or cooling of the reagent container before dispensing (e.g., refrigeration of container for cooling, oven or hot plate for heating), external heaters or ribbon heaters wrapped around a conduit between the container and a respective conduit.

115 115 1151 121 120 1155 1157 1157 115 1 FIG. An example of a bulk reagent is a wash solution such as water or a water and surfactant and/or buffer mixture. A wash solution may be used to wash the sample on the microscope slide, the entire microscope slide or slide bed(with or without a microscope slide thereon). Representatively, to wash slide bedwith or without a microscope slide on platform, a wash solution may be introduced through openingin a top of body(see) to contact rampwhich allows the wash solution to flow directly in gutterwithout going on the microscope slide. The wash solution in guttereventually will drain out from an opening(s) in a base of slide bedeither while the slide bed is horizontal or when it is tilted (or both).

125 120 125 Bulk reagents dispensed into chamberof bodymay be dispensed at below ambient temperature, ambient temperature or elevated (above ambient) temperature. An elevated temperature may be achieved by, for example, heating the conduit that transfers the reagent into chamber(e.g., a resistive heater around the conduit with output controlled by instructions from a controller) or by having a separate reservoir for pre-heating the reagent to a determined elevated temperature.

125 120 130 120 120 115 125 125 130 115 125 125 130 155 115 125 In one example, the reagent dispense of primary reagents may take place with the sample and at least a portion of the microscope slide containing the sample outside of the chamberof body. Representatively, doorof bodymay be moved from a closed position to an open position. With doorin an open position, slide bedmay be moved from a position inside chamberto a position outside chamber. The opening of doorand the movement of slide bedfrom a position inside chamberto a position outside chambermay be controlled by a controller including non-transitory, machine-readable instructions to initially open doorand then direct linear actuatorto move slide bedto a position outside chamber.

115 125 Once a portion of slide bedincluding microscope slide including a tissue sample is outside chamber, a reagent dispense may be performed by various methods. Such methods include, but are not limited to, overhead dispensing through a thermal or piezoelectric inkjet printhead, through a spray nozzle, through a micro-electromechanical dispense mechanism, through puncturing a reagent vessel and drip mechanism. Examples of dispensing through a thermal or piezoelectric inkjet printhead are described in U.S. Patent Publication 2023/0055997 (Ser. No. 17/790,040) titled “Automated Staining System and Reaction Chamber” which is incorporated herein by reference. Examples of dispensing through a spray nozzle and through a puncturing a reagent vessel and drip mechanism are described in U.S. Pat. No. 10,295,444 (Ser. No. 14/579,858) titled “Automated Staining System and Reaction Chamber” which is incorporated herein by reference.

115 A microscope slide may be placed with a sample facing up (away from the slide bed) or facing down (facing the slide bed). Reagent dispense from above, either a bulk reagent or primary reagent, may be directly onto the sample or onto the slide when the sample is facing up or onto slide bedwhen the sample is facing down so that the reagent can migrate to the sample through capillary action.

112 125 120 158 125 158 159 120 From time to time, excess reagent including wash solution may be drained from sample processor. As noted above, extending from chamberthrough a base wall of bodyis conduitthat may serve as a drain to drain the fluid contents of the reservoir in chamber. Conduitis connected at a distal end to drain valveoutside body.

6 FIG. 200 202 200 202 204 201 204 201 205 204 205 205 205 208 210 204 illustrates a perspective view of an embodiment of a sample processing system. Sample processing systemincludes housingfor enclosing and storing various components of processing system. Housingincludes reaction compartmentand storage compartment. Reaction compartmentis separated from storage compartmentby platformthat forms a base of reaction compartment. In addition to platform, opposing sidewalls project from platformand a cover connects an end of each of the sidewalls. Together, the cover, sidewalls and platformdefine a compartment within which sample processing occurs. Cover memberand door membermay be used to gain access to components within reaction compartment.

204 206 205 204 206 206 206 Reaction compartmentis dimensioned (e.g., has an interior volume) to accommodate a storage rack to store a number of reagent cartridges. Storage rackmay be mounted on platformor to one of the sidewalls of reaction compartment(e.g., a rear sidewall as viewed). Storage rackmay be used to store reagent cartridges. A representative reagent cartridge is a single use cartridge, such as an inkjet cartridge that contains a volume of a reagent that may be used in pathological or histological processing. Storage rackcontains an array of slots to store individual reagent cartridges in, for example, a column and row array. Storage rackmay include refrigeration to store reagent cartridges in a refrigerated state. Representative refrigeration may include a compressor that constricts a refrigerant vapor and pushes the vapor through coils where it liquifies and cools the storage rack slots.

204 112 112 112 205 204 112 214 215 215 112 215 214 112 206 1 5 FIGS.- 6 FIG. Reaction compartmentis dimensioned to accommodate a plurality of sample processorstherein. Each sample processormay be as described above with respect toand the accompanying text.representatively shows 30 sample processorsarranged in a planar (an xz plane) in a 15×2 configuration on platform. It is appreciated that the number of sample processors and configuration will depend in part on the area dedicated to reaction compartment. It is thus contemplated that the number of sample processors may vary as may their configuration. Disposed above sample processorsas viewed is a carousel assembly including gantryand carousel. Carouselis operable to house/contain a number of reagent cartridges and dispense reagents from respective reagent cartridges onto respective slides in a sample processor. Carouselis operable to move on gantryto position a reagent cartridge over individual sample processorsas well as to load/unload reagent cartridges from/to storage rack.

200 209 209 206 215 209 202 209 202 202 6 FIG. Sample processing systemalso includes controller. Controllerincludes non-transitory machine-readable instructions to control an operation of sample processing system including, but not limited to, loading/unloading reagent cartridges in storage rackand loading/unloading reagent cartridges in carousel.shows controlleroutside of housing. It is appreciated that controllermay be outside housingor a component inside housing.

6 FIG. 112 112 112 130 206 112 130 206 130 125 120 112 105 104 102 representatively shows 30 sample processorarranged in a planar (an xz plane) in a 15×2 configuration with the sample processorsin a row arranged in a back-to-back configuration with respect to the other row. A first of the two rows may have sample processorseach having doorfacing outward (away from storage rack). A second of the two rows may have sample processorseach having doorfacing inward (toward storage rack). The back-to-back configuration allows each doorof a sample processor to be moved to an open position and a slide bed of the sample processor to be positioned outside a chamberof bodyof a sample processor as described above. Each sample processormay be connected to platformof reaction compartmentof housing.

6 FIG. 7 FIG. 112 204 202 200 214 115 214 215 214 2142 204 2142 112 204 2142 112 2144 2144 2142 204 2144 2142 2145 2144 215 2144 2145 2146 2146 2144 2147 2147 2146 2146 2144 2146 2148 2146 21493 21493 21493 2140 2146 Referring to, in addition to sample processors, reaction compartmentof housingof processing systemalso includes gantrythat supports carousel. Gantryand carouselcollectively describe a carousel assembly.shows a perspective left side view of the carousel assembly in isolation. Gantryincludes two vertical (y-direction) postsconnected to a base of reaction compartment. Vertical postsare separated by an x-direction distance greater than a distance covered by a row of sample processorsin reaction compartment. Disposed between vertical postsat a position above sample processorsare two horizontal supports. Horizontal supportsare representatively each cylindrically shaped and extend the x-direction distance of vertical postsand are each parallel to a base of reaction compartment. Horizontal supportsare connected to vertical postsby end brackets(e.g., inverted L-shaped brackets). Horizontal supportsare separated by a z-direction distance chosen for a z-direction travel of carouselas will be detailed below. Connected to each of horizontal supportsbetween end bracketsis U-shaped bracket(e.g., an inverted U-shape as viewed). U-shaped bracketincludes two legs separated by a base. Horizontal supportsare connected to the base by linear bearings. Linear bearingsare connected to an upper or exposed side of the base of U-shaped bracketand allow U-shaped bracketto move in an x-direction on horizontal supports. A base of U-shaped bracketincludes openingtherethrough, such as a rectangular-shaped opening. Also connected at one end of the upper or exposed side of the base of U-shaped bracketis tab. Tabprojects upward (in a y-direction) from the base. Tabis connected to timing beltthat is used to move U-shaped bracketin an x-direction (longitudinal direction).

2146 2144 2149 2149 2149 21499 2149 2146 2149 2146 2149 2146 2149 21492 215 21492 Connected to the base of U-shaped bracketbelow horizontal supportsis transversal drive support bracket. Transversal drive support bracketis U-shaped (e.g., an inverted U-shape as viewed) defined by a base and sidewalls. A top side of transversal drive support bracketas viewed has openingtherethough. The base of transversal drive support brackethas a x-direction width that is less than a corresponding width of the base of U-shaped bracketso that the sidewalls of transversal drive support bracketare positioned between the sidewalls of U-shaped bracketand the sidewalls of transversal drive support bracketare connected to the respective sidewalls of U-shaped bracketvia, for example, screws, rivets, or welds. On an inside of each of the sidewalls of transversal drive support bracketis a transversal linear guide that extends a z-direction length of the sidewalls or 70 percent to 90 percent of the z-direction length. Each transversal linear guideis at a similar y-direction distance from an end of a sidewall connected to the sidewall by, for example, screws, rivets, welds. Carouselis connected to each transversal linear guide.

215 214 215 2146 215 2145 2142 215 215 21492 2149 Carouselcan move in three directions on gantry. Carouselcan move in an x-direction (longitudinal) with the movement of U-shaped bracket. Carouselcan move in a y-direction (vertical) with the movement of end bracketsup or down vertical posts. Carouselmay move in a z-direction (transversal) with the movement of carouselalong each transversal linear guidein transversal drive support bracket.

8 FIG. 8 FIG. 7 FIG. 214 214 2144 2142 2145 214 2141 2141 2143 2141 2144 2140 2140 2141 2140 21493 2146 2140 2146 2143 2146 2149 115 shows a perspective right side view of a portion of gantryto illustrate the x-direction (longitudinal) drive mechanism. In this view, gantryincludes horizontal supportsconnected to vertical postsby end brackets. Connected to the top of each end bracket on one side of gantry(left side as viewed in) are gearsthat rotate in an xz plane. One of gearsis connected to a shaft of motorwith the motor operable to rotate the one gear in a clockwise or counterclockwise direction. Disposed around gearsand extending above one of horizontal supportsis timing belt. Timing beltis operable to move in an x-direction (longitudinal direction) by gears. Timing beltis connected to tabattached to U-shaped bracketvia screws, rivets, pins, etc. (see). The connection of timing beltto U-shaped bracketallows motorto move U-shaped bracketand, consequentially, transversal drive support bracketand carouselin an x-direction′ (longitudinal direction).

9 FIG. 9 FIG. 7 FIG. 6 FIG. 7 FIG. 2146 2149 2147 2146 2147 2144 2147 2146 2144 2147 2144 2144 2146 2148 2147 2147 2146 21493 21493 21493 2140 2146 shows a perspective rear side view of U-shaped bracketand transversal drive support bracketin isolation.shows linear bearingsare connected to an upper or exposed side of the base of U-shaped bracket. Linear bearingssupport horizontal supports(see). Three linear bearingsare shown with one linear bearing on one end of U-shaped bracketto support one horizontal supportand two linear bearingson an opposite end of the base to support the other horizontal support, with the z-direction separation of the one linear bearing from the two linear bearings equivalent to a z-direction distance between horizontal supports(see). A base of U-shaped bracketincludes openingtherethrough, such as a rectangular-shaped opening, between the one linear bearingand the two linear bearings. Also connected at one end of the upper or exposed side of the base of U-shaped bracketis tab. Tabprojects upward (in a y-direction) from the base. Tabis connected to timing beltthat is used to move U-shaped bracketin an x-direction (longitudinal direction) (see).

9 FIG. 9 FIG. 2149 2146 21494 21494 2149 2149 21492 21494 21494 also illustrates the z-direction (transversal) drive mechanism.shows transversal drive support bracketconnected to U-shaped bracketand positioned under the U-shaped bracket. On an inside of each of sidewallA and sidewallB of transversal drive support bracketis a transversal linear guide that extends a portion of the z-direction length of the sidewalls of transversal drive support bracket(e.g., 70 percent to 90 percent of the z-direction length). Each transversal linear guideis at a similar y-direction distance from an end of a sidewall (sidewallsA andB) connected to the sidewall by, for example, screws, rivets, welds.

9 FIG. 9 FIG. 21493 21494 2149 21493 21494 2149 21493 21494 2149 21493 21493 21496 21495 21495 21493 21494 2149 21497 21497 21493 The z-direction (transversal) drive mechanism illustrated inalso includes two gearsconnected to the exterior of sidewallA of transversal drive support bracket(left sidewall as viewed). In, only one of two gearscan be viewed at one end (a rear end) of sidewallA of transversal drive support bracket. A second of two gearsis located at the opposite end (a front end) of sidewallA of transversal drive support bracket. Each of two gearsrotates in yz plane. One of two gearsis connected to worm gearthat is rotated by a shaft of motorwith motoroperable to rotate in a clockwise or counterclockwise direction. Disposed around gearsand extending along sidewallA of transversal drive support bracketis timing belt. Timing beltis operable to move in an z-direction (transversal direction) by gears.

10 FIG. 9 FIG. 9 FIG. 215 215 2149 214 215 21510 2149 21511 21514 21512 21513 21510 21515 2151 21512 21510 2153 21531 21512 21532 21533 21532 2153 21512 21532 21533 2149 21494 21510 2149 21497 2153 21495 21510 215 21512 2154 21492 21494 2149 21513 21512 2159 2159 21492 21494 2149 is a perspective rear side view of a portion of carousel. Illustrated in this view is a portion of carouselthat connects to transversal drive support bracketof gantry. Carouselincludes rectangular shaped main brackethaving a length dimension (x dimension) and a width dimension (z dimension) defined by opposing pairs of sidewalls to be positioned within transversal drive support bracket. Sidewalland sidewalldefine a length dimension and sidewalland sidewalldefine a width dimension. Main bracketalso includes top portionconnected to each sidewall and having an opening therethrough for column. Connected to sidewallof main bracketis z-shaped brackethaving baseprojecting horizontally away (x direction) a distance, d, from sidewall; midportionprojecting vertically (y direction); and apexprojecting horizontally away (x direction) from midportion. The projection of z-shaped bracketaway from sidewalla distance, d, allows midportionand apexto be positioned on an exterior side of a sidewall of transversal drive support bracket(sidewallA) when main bracketis positioned within transversal drive support bracket. Timing belt(see) is connected to apex(via, for example, screws, rivets, pins, etc.) which allows motorto move main bracketof carouselin a z-direction (transversal direction). Also attached to sidewallare transversal slide bearingsoperable to engage with transversal linear guideconnected to an inside of sidewallA of transversal support bracket(see). Projecting outward from sidewall(opposite sidewall) is roller. Rolleris operable to engage and rotate in a yz plane within transversal linear guideof sidewallB of transversal drive support bracket.

21510 21515 2151 2151 21515 21510 2155 2155 2151 2155 2156 2156 2155 2151 21510 2156 2157 2157 21515 21510 2158 2156 2156 2151 215 2152 2151 2157 2152 7 FIG. As noted, main bracketincludes top portionhaving an opening therethrough for column. Columnincludes cut or inserted teeth around a top portion thereof. Disposed on top portionof main bracketis slew bearing. Slew bearingincludes an outer ring and an inner ring, the inner ring incorporating a gear with cut or inserted teeth that mesh with the teeth around a top portion of column. Disposed on a top surface of slew bearingand connected thereto is gear. Gearis operable to rotate in a xz plane and to rotate the inner ring of slew bearingin the same plane and consequently rotate column. Main bracketremains stationary (does not rotate). Gearis rotated by motor. Motoris mounted to top portionof main bracketand has a shaft extending therefrom that rotates in a yz plane. The shaft is connected to worm gearthat meshes with gearto rotate gearin an xz plane. Referring to, a base of columnof carouselincludes pedestal or cartridge carrier platethat is operable to engage and contain a number of reagent cartridges. Rotation of columnby motorrotates pedestal.

7 FIG. 214 2142 2142 21422 21424 21424 2145 21425 21424 2145 2144 215 Referring again to, gantryincludes two vertical posts. Vertical postsare shown with rectangular housingdisposed around lead screws. Each lead screwis connected to a respective end bracketand is driven (rotated clockwise or counterclockwise) by a respective stepper motor (motor) with one stepper motor slaved to the other. The rotation of the lead screwsprovides y-direction movement of end bracketsand, correspondingly, horizontal supportsand carousel.

215 214 215 2146 2143 215 2145 2142 21425 215 215 21492 2149 21495 2143 21425 21495 209 As noted above, carouselcan move in three directions on gantry. Carouselcan move in an x-direction (longitudinal) with the movement of U-shaped bracketby motor. Carouselcan move in a y-direction (vertical) with the movement of end bracketsup or down vertical postsby stepper motors. Carouselmay move in a z-direction (transversal) with the movement of carouselalong each transversal linear guidein transversal drive support bracketdriven by motor. Each of motor, stepper motorand motoris controlled by non-transitory machine-readable instructions in controllerthat directs their operation (e.g., direction of rotation, run time, etc.).

215 2152 215 218 218 214 215 218 2182 21511 21510 21511 2182 2184 2182 2186 2186 2182 2184 2182 2186 2186 2183 2183 7 FIG. 11 FIG. 10 FIG. 7 FIG. Carouselis operable to automatically load/unload and engage or accommodate/disengage or disaccommodate a number of reagent cartridges on pedestal. Referring to, carouselcan automatically load/unload reagent cartridges through the use of arm assembly.shows a side perspective view of arm assemblyisolated from gantryand carousel. Arm assemblyincludes attachment bracketmounted via, for example, bolts, screws, rivets or pins to exterior surface of sidewallof main bracket(e.g., mounted at a midpoint of sidewall(see)). Connected to a top of attachment bracketis short actuatorand to a bottom of attachment bracketis long actuator. In, long actuatorprojects approximately perpendicularly (horizontally as viewed) from attachment bracketand short actuatorprojects approximately diagonally (e.g., projects at a 45 degree angle) from attachment bracketto connect with long actuator. Connected to an end of long actuatoris cartridge engagement head. Cartridge engagement headhas pairs of fingers on opposite sides thereof that are separated by a distance, di, that allows the fingers to surround a protrusion of a reagent cartridge (described below) and engage and move the reagent cartridge.

11 FIG. 2182 21822 21823 2184 21822 2186 21823 2184 2186 2184 2186 2185 2185 2183 2184 2186 2184 2184 2186 21823 2186 21822 2186 2184 2186 21822 shows a top portion of attachment bracketincludes clevis portionand a bottom portion includes clevis portion. One end of short actuatoris connected to clevis portionwith, for example, clevis pin, screw or bolt in a manner that it can rotate about the pin, screw or bolt. Similarly, one end of long actuatoris connected to clevis portionwith, for example, clevis pin, screw or bolt in a manner that it can rotate about the pin, screw or bolt. Each of short actuatorand long actuatorincludes an electrically actuated telescoping body (e.g., a three-stage body of successively smaller cylinders or pillars). A second end of short actuatoris connected to the smallest stage or plunger of long actuatorthrough linkage. Linkageis proximal to engagement head. The connection position of short actuatorto long actuatoris selected such that when short actuatoris fully retracted, short actuatorwill rotate long actuatora few degrees (e.g., up to 10 degrees, such as 2 degrees to 8 degrees) about clevis portioncausing a distal end of long actuatorincluding engagement head to move toward clevis portion(to be lifted). Long actuatorcan be extended in the lifted configuration to a position over a reagent cartridge. Short actuatorcan then be extended to rotate long actuatorin an opposite direction (i.e., rotate long actuator away from clevis portion) to lower engagement head onto a reagent cartridge to grasp the reagent cartridge.

6 FIG. 12 FIG. 12 FIG. 12 FIG. 200 202 200 206 206 217 206 202 206 2062 204 215 206 206 206 217 209 215 209 217 As noted above and illustrated in, sample processing systemincludes housingfor enclosing and storing various components of processing systemincluding storage rack. Storage rackmay be used to store reagent cartridges (e.g., reagent cartridge).shows a perspective front left side view of storage rackisolated from other components of housing. Storage rackincludes housingthat includes slots facing reaction compartmentand carousel. Storage rackcontains an array of slots to store individual reagent cartridges.shows an array of five rows and 25 to 30 columns of slots. An array of rows and columns allows each slot to have an address (e.g., designated by row and column number) so that the system can know a location of a reagent cartridge and find a reagent cartridge in storage rackor return a reagent cartridge to a particular slot in storage rack. In, reagent cartridges (reagent cartridge) are seated in all slots of the array. An exterior surface of each reagent cartridge may contain an identifier such as a barcode that contains identifying information about the reagent contained in the reagent cartridge and possibly other information such as an expiration date. The identifier may be read by a reader (e.g., a barcode reader) and the read information electronically provided to controller. One example is a reader on carouselthat is electronically linked to controller. An identifier on a reagent cartridge (e.g., reagent cartridge) can have a re-writable IC chip which can store the identity of the reagent, a lot number, an expiration date, and usage count.

13 FIG. 217 206 200 217 217 217 217 2 1 shows a side perspective view of reagent cartridgethat is representative of reagent cartridges operable for storage in storage rackand use in sample processing system. Representatively, reagent cartridgehas a z-direction depth on the order of 67.4 millimeters (mm), an x-direction width of 5 mm to 10 mm and a y-direction height of 98.5 mm. In another example, reagent cartridgehas a similar depth and width and a height of 70.8 mm (His less than H). Reagent cartridgemay be drop on demand-type (e.g., inkjet) cartridge, such as a thermal drop-on-demand type cartridge or a piezoelectric drop-on-demand type cartridge with the reagent cartridge including an individual dedicated printhead positioned at a base of reagent cartridgeas viewed.

217 217 2171 217 2172 2173 2174 2175 2174 215 217 2178 2178 2179 217 215 2179 2179 2178 2179 2178 217 13 FIG. 13 FIG. Reagent cartridgemay contain a volume of a reagent and have a dedicated printhead. Each cartridge may be a single use cartridge. A single use cartridge in this context means that once the volume of the reagent in the cartridge is dispensed or used, the cartridge including its printhead is to be discarded or disposed of as opposed to being resupplied with a volume of reagent. A reagent cartridge may include (be supplied with) a volume of a reagent suitable for dispensing the reagent on one or more than one sample (e.g., tissue sample) on a slide. An example of a single use cartridge is a thermal inkjet cartridge. Referring to, reagent cartridgeincludes outer shell or bodyhaving a generally rectangular shape constructed of a plastic material (e.g., a hard plastic or polymer).shows reagent cartridgeincluding sideand opposite sidethat represent yz-dimensions as well as sideand opposite sidethat represent xy-dimensions. Sidecontacts and engages with carousel. Reagent cartridgeincludes printheadoperable to discharge a reagent from the cartridge. Printheadmay be positioned at or near snout or baseof reagent cartridge(a bottom side as viewed) so that when the reagent cartridge is inserted in carousel, the ejection of reagent occurs through baseof the reagent cartridge. The portion of snout or baseincluding printhead(a printhead area) may extend below a remainder portion of basein a step-like manner. Printheadof reagent cartridgeincludes a nozzle or an array of nozzles through which reagent is ejected or discharged through an inkjet process (e.g., a thermal inkjet process). A representative array of nozzles is a linear array (e.g., a single row or multiple rows) of nozzles allowing discharge of a reagent in a line(s) or row(s), such as across a microscope slide. In a thermal inkjet printhead, heat may be used to create an air bubble of reagent vapor that is exploded as it is forced through a printhead nozzle. Each nozzle may have a diameter on the order of 20 microns to 80 microns, such as 20 microns to 50 microns.

217 2170 2174 2170 2170 209 15 FIG. Reagent cartridgealso includes contactson side. Contactsare designed to mate with contacts in docks associated with a carousel (see) and the associated text). Contactsallow reagent cartridge to be controlled by controllerregarding, for example, discharge or firing of reagent through nozzles and the amount of reagent discharged.

217 2172 2173 2172 2173 2176 2172 217 2176 217 106 2176 21762 2176 2171 2171 2172 2176 21762 217 2177 2171 2171 217 2176 2176 2172 217 217 206 1176 2177 2176 2172 2176 2176 2177 2174 217 2177 21772 21774 21772 21774 2177 217 21792 2172 2173 2176 2177 21792 217 217 13 FIG. 1 1 1 1 1 2 2 2 2 1 2 3 2 Reagent cartridgeshown inincludes a pair of transfer guides on each of sideand side. The transfer guides on sideare described, but it is appreciated that the transfer guides on sideare similar. Transfer guidehas a generally rectangular solid structure of, for example, a plastic material and has a width, W, that extends across the width of sideparallel to a top surface of reagent cartridge. Transfer guidehas a thickness, T, and length, L, sufficient to support reagent cartridgein storage rack. A representative thickness, T, is on the order of 0.2 millimeter (mm) to 1 mm and a representative length, L, is on the order of 3 mm to 10 mm. Transfer guideincludes engaging protrusionthat projects vertically upward as viewed from a top side of the transfer guide. As illustrated, transfer guideis connected to the body(e.g., via adhesive) or is part of bodya distance from a top of sideas viewed such that the entirety of transfer guideincluding engaging protrusionis below the top surface of reagent cartridge. Transfer guideis connected to body(e.g., via adhesive) or is part of bodyof reagent cartridgeat a position below transfer guideas viewed. Transfer guidehas a width, W, that extends across the width of sideparallel to a top surface of reagent cartridge, a thickness, T, and length, L, sufficient to support reagent cartridgein storage rack. A representative thickness, T, is similar to a thickness, T, of transfer guide, e.g., on the order of 0.2 mm to 1 mm and a representative length, l, is on the order of 3 mm to 8 mm. Transfer guideis arranged parallel to transfer guidealong sideand is separated from transfer guideby a gap, L, sufficient for an arm of a cartridge support to slide between the transfer guides. Each of transfer guideand transfer guidemay have a rounded or curved front end (end closest to sideof reagent cartridge) to aid the positioning of an arm of a cartridge support between the transfer guides. A base of transfer guidealso includes notch or docking grooveas well as thinned portion(thickness less than a thickness, t) from the front end of transfer guide to a point just forward (1 mm or 2 mm forward) of notch or docking groove. Thinned portionmay have a rear angled sidewall from the top of transfer guidetoward the base. Finally, reagent cartridgeincludes frame locking bumpthat is a triangular prism with triangular bases parallel with sideand, respectively. Each of transfer guide, transfer guideand frame locking bumpmay be made of a hard plastic material that is either attached to reagent cartridgeby, for example, adhesive, or is part of reagent cartridgeformed, for example, by way of a mold process.

14 FIG. 14 FIG. 14 FIG. 206 206 2064 2063 206 202 204 215 2064 20642 20642 2064 2065 20642 2064 217 217 2064 2064 2060 217 2060 2064 217 shows a perspective front right side view of a portion of storage rack. In this view, storage rackincludes cartridge frame supportextending between vertical posts. Storage rackis mounted to housingwith slots facing reaction compartmentand carousel. Cartridge frame supportis an L-shaped body with baseof the L-shaped body facing outward. Disposed in baseof frame supportare pairs of openings or holesthrough basethat will be used to secure reagent cartridges to frame support.shows reagent cartridgeA and reagent cartridgeB connected to cartridge frame support. Reagent cartridges are connected to cartridge frame supportutilizing a cartridge frame.shows cartridge frameB supporting reagent cartridgeB and cartridge frameC connected to cartridge frame supportbut not supporting a reagent cartridge. It is appreciated that a separate cartridge frame is supporting reagent cartridgeA but such cartridge frame is blocked from view.

2060 2060 20602 20602 20605 2065 20642 2064 20602 20642 2064 20601 20603 2065 20642 2064 20603 20602 20642 2064 2060 2060 20642 2064 Each cartridge frame (e.g., cartridge frameB and cartridge frameC) includes shoulderthat is a relatively thin (e.g., 1 mm to 3 mm) rectangular body that has an x-direction length greater than a width of a reagent cartridge. Shoulderhas two openings or holesthat can be aligned with pairs of openings or holesin baseof frame supportto allow shoulderto be connected to baseof cartridge frame supportthrough the use of pins. Pinsare, for example, expander pins (e.g., plastic) with a distal end and body that projects from the cartridge frame and the distal end is operable to slide into an opening or holeand the body having a similar or greater diameter than the opening or hole to secure the pin through the application of a force in the direction of baseof cartridge frame support. Pinsmay be captive pins, meaning the pins are permanently secured to the cartridge frame, or may be free to be introduced into both shoulderof the cartridge frame and baseof cartridge frame support. Each cartridge frame (e.g., cartridge frameB and cartridge frameC) is designed to be removable from baseof cartridge frame supportthrough the use of a similar but opposite force required to insert the pins.

20602 20603 20603 2176 2177 20603 20603 20603 20602 20602 20606 20606 2177 20606 20607 217 20607 20607 20608 20607 20608 20607 20606 217 21792 217 2069 20608 20607 20609 20609 20609 14 FIG. 13 FIG. 2 2 Projecting perpendicularly from shoulderas viewed (x-direction) are two arms. Each armhas dimensions (e.g., a y-direction height and x-direction thickness) that allows an arm to fit between transfer guideand transfer guideon each side of a reagent cartridge in a manner that the reagent cartridge can slide into and out of the cartridge frame. Armsare separated from one another by a distance slightly greater than a width of a reagent cartridge (e.g., where a reagent cartridge has a width of 6 mm, armsare separated from one another by 6.3 mm to 7 mm). Armshave a length (z-direction) measured from shoulderof less than a depth of a reagent cartridge, such as a length approximately one-half the depth of a reagent cartridge. Projecting vertically downward as viewed from shoulder(y-direction), each cartridge frame includes spine. Spinehas a representative width (x-direction) on the order of 1 mm to 4 mm, a thickness (z-direction) on the order of 0.4 mm to 0.5 mm and a length (y-direction) that is longer than a height of a portion of reagent cartridge measured between a base of the reagent cartridge behind the printhead area and a bottom of transfer guidethereon, such as a 1 mm to 2 mm longer. Projecting perpendicularly from a base of spine(z-direction) is leg. A shape at the spine-leg interface may mirror a transition of a rear sidewall and a base of a reagent cartridge. In, a transition of a rear sidewall and a base of reagent cartridgeB is curved and the spine-leg interface defines an opposite profile. Legmay have a thickness (y-direction) on the order of 0.5 mm to 1.5 mm; a width (x-direction) of 1 mm to 3 mm; and a length (z-direction) that extends a length of a base of a reagent cartridge exclusive of the printhead area. Disposed along a portion of the length dimension of legis protuberancethat projects upward from a surface of legrepresentatively 0.2 mm to 0.6 mm and has a representative shape of a triangular prism with triangular bases in a yz plane. Protuberanceis located on lega distance from spinethat is greater than a distance from the rear side of a reagent cartridge (reagent cartridge,) to a forward edge of frame locking bumpso that when a reagent cartridge is positioned in cartridge frame (e.g., reagent cartridgeB in cartridge frameB), protuberanceis forward of the frame locking bump projecting from a base of the cartridge. Connected at an end of legof a cartridge frame is pad platform. Pad platformmay be rectangular body having a rectangular face or top (xz plane) that is larger than a printhead area. A representative area (xz dimensions) for pad platform is on the order of 225 mmto 400 mm. Disposed on the face or top of pad platformmay be an absorbent material (e.g., sponge) that can contact a printhead of a reagent cartridge, accept outflow from the printhead (e.g., excess reagent on a surface of printhead), and protect the printhead from drying out.

2060 2060 20606 20607 20607 20607 21792 217 20606 20603 2176 2177 21792 20608 20606 20607 21792 20608 21792 20608 21792 20608 20607 20607 20606 20607 21792 20608 21792 20608 14 FIG. 13 FIG. A body of a cartridge frame (e.g., cartridge frameB, cartridge frameC) may be made of a hard plastic material. Referring to, spineand legmay have dimensions (e.g., thickness, width) and/or a connection (e.g., 90° junction) that provide legwith give or a spring tension so that legmay move when a reagent cartridge is connected or removed. As noted above, a reagent cartridge includes frame locking bumpprojecting from its base (see reagent cartridge,). When a reagent cartridge is placed into a cartridge frame (i.e., in response to a force applied to the reagent cartridge in a direction toward spineof the cartridge frame), armsof the cartridge frame slide between transfer guidesandon respective opposing sides of the cartridge until frame locking bumpat the base of the reagent cartridge contacts protrusion. Continued force in a direction toward spinewill cause legto move downward (by the force of frame locking bumpon the leg) causing protrusionto be moved downward and frame locking bumpto pass protrusion. Once frame locking bumpis past protrusion, legwill return to its original position (move upward) allowing protrusionto secure or capture the reagent cartridge in the cartridge frame. Separating a reagent cartridge from a cartridge frame is achieved in a similar manner. A force on the reagent cartridge in a direction away from spinewill cause legto move downward (by the force of frame locking bumpon the leg) causing protrusionto be moved downward and frame locking bumpto pass protrusion.

217 217 2060 2060 Reagent cartridges (e.g., reagent cartridgeA, reagent cartridgeB) may be provided as an assembly including the reagent cartridge and the cartridge frame (e.g., cartridge frameB, cartridge frameC). The assembly may be provided to a consumer together in a package with the reagent cartridge in the cartridge frame or separate and with instructions for assembly.

7 FIG. 11 FIG. 12 FIG. 14 FIG. 13 FIG. 11 FIG. 218 206 204 205 204 209 215 218 206 2143 215 21495 215 21425 215 2157 2152 215 218 215 206 206 218 2183 2183 209 217 2183 21762 2176 217 2183 218 21762 217 2183 21762 217 2183 21762 206 218 20603 20605 20642 2064 20642 2064 Referring to,,and, arm assemblymay be used to move reagent cartridges into and out of storage rack. As one example, a reagent cartridge assembly (reagent cartridge connected to cartridge frame) may be delivered to reaction compartment(e.g., delivered to platforminside reaction compartment) by an operator or a robot. Controllerincludes non-transitory, machine-readable instructions that direct an operation of the various motors (e.g., direction of rotation, run time, etc.) to bring carouselincluding arm assemblyto a position to grasp a delivered reagent cartridge assembly and place that reagent cartridge assembly in storage rack. These motors include motorthat moves carouselin an x-direction; motorthat moves carouselin a z-direction; motorthat moves carouselin a y-direction; and motorthat rotates pedestal. When carouselis positioned as desired, the machine-readable instructions also include instructions to direct arm assemblyconnected to carouselto grasp the reagent cartridge assembly and transport the reagent cartridge assembly to storage rack. The instructions may further include instructions to place the reagent cartridge assembly at a predetermined address in storage rack. Arm assemblyincludes cartridge engagement headat its distal end. Cartridge engagement headis operable based on instructions from controllerto be brought to a position over reagent cartridgeso that the pairs of fingers extending from cartridge engagement headsurround and engage engagement protrusionof transfer guideon each side of reagent cartridge(see). The pairs of fingers on cartridge engagement headof arm assembly(see) may be spaced (separated) on opposite sides by a distance that is slightly less than a distance between engagement protrusionson each side of reagent cartridge. Representatively, the pairs of fingers on cartridge engagement headare biased to their separated distance but can flex outward a greater distance to engage engagement protrusionson opposite sides of reagent cartridge. The biased nature of the opposing fingers on cartridge engagement headact like a spring clamp to hold a reagent cartridge by engagement protrusions. To place the reagent cartridge assembly into storage rack, the instructions direct arm assemblyto align pinsin the cartridge assembly with a determined pair of openings or holesin baseof frame supportand apply enough force to the reagent cartridge assembly to insert the pins in the corresponding in baseof frame support.

206 215 209 2183 21762 2176 217 206 2183 21762 2176 217 218 20606 20607 21792 217 20607 20608 21792 20608 209 218 215 To transfer a reagent cartridge from storage rackto carousel, controllerincludes machine-readable instructions that direct arm assembly to be positioned at a reagent cartridge (e.g., a front side of the reagent cartridge) and to grasp the reagent cartridge (via cartridge engagement headsurrounding and engaging protrusionof transfer guideon each side of reagent cartridge). At this point, the reagent cartridge assembly including a reagent cartridge and a cartridge frame are mounted in storage rack. Once cartridge engagement headgrasps engaging protrusionsof transfer guideon each side of reagent cartridge, arm assemblyapplies a force in a direction away from storage rack (and away from spineof the cartridge frame) to deflect legof the cartridge frame (cause to move downward) by the force of frame locking bumpof reagent containeron legcausing protrusionto be moved downward and frame locking bumpto pass protrusion. Once the cartridge is separated from its cartridge frame, instructions associated with controllerdirect arm assemblyto deliver the cartridge to carousel.

15 FIG. 15 FIG. 15 FIG. 13 FIG. 215 2152 2151 2152 2152 2153 2153 2154 2152 2154 2152 2154 217 2154 2154 2152 2152 2176 2177 21542 21544 21544 21544 2176 2177 217 2154 21544 d shows a portion of carouselincluding pedestal or cartridge carrier plateisolated from a base of column. Pedestal or cartridge carrier plateis operable to engage and contain a number of reagent cartridges. Pedestalhas a representative decagon shape with slotsin each side for a reagent cartridge. It is appreciated that the shape and the number of reagent cartridges that a carousel may accommodate may vary. Surrounding each slotis dockthat projects from a surface of pedestal(upper surface as viewed).shows three docks. It is appreciated that pedestalmay have as many docks as slots. Each dockis configured to contain a reagent cartridge therein.shows reagent cartridgestationed in one dock. Each dockincludes a back wall with an exterior surface facing a center of pedestaland two opposing sidewalls connected to the back wall. The back wall is inclined from top to bottom with the bottom of the back wall closer to a center of pedestal. The sidewalls have a thickness, t, that is less than a thickness of transfer guidesandon a reagent cartridge (see). An upper portion of each sidewall contains a lateral slotthat extends from a distal end of the sidewall to a portion near a proximal end (near but not to the back wall) to define arm portion. Each arm portionhas dimensions to allow arm portionto be positioned between transfer guidesandon reagent containerand support the reagent container. Dockincluding arm portionsmay be constructed of a plastic (polymer) material.

2154 2170 217 209 209 2154 215 An interior surface of a back wall of each dockincludes contacts that mate with contactson a reagent cartridge (reagent cartridge). The contacts are electrically connected to controllerallowing controllerto individually control a reagent cartridge in each dockon carousel.

2154 21544 2155 2155 21552 21554 21554 2154 21552 2154 21552 21555 21552 21554 21555 21552 21555 21554 2155 2154 21554 2154 21554 21552 21554 21552 21552 21556 21556 21772 2177 2155 2155 2152 21556 21544 2154 21556 15 FIG. 13 FIG. Connected to the two opposing sidewalls of each dockat a point below arm portionsas viewed is cartridge lock. Cartridge lockincludes two parallel armsseparated by shoulder. Shoulderhas a width similar or slightly greater than a width of dockso that armsmay be positioned and connected to an exterior of respective opposing sidewalls of dock.shows armconnected to a sidewall by pin(for example, a pin, screw or rivet) such that a length of a portion of each armfrom shoulderto pin(a distal portion) is greater than a length of a portion of each armfrom pinto a proximal end (an end furthest from shoulder). The connection of cartridge lockto dockis such that shouldercan pivot upward and downward as viewed without contacting the back wall of dock(e.g., shoulderis 0.1 mm to 0.5 mm from an exterior surface of the back wall). A distal portion of each armis generally rectangular and projects proximally perpendicularly from shoulder. A proximal portion of each armmay project at an angle upward relative to the distal portion so that an angle, γ, defined between a distal portion and a proximal portion is on the order of 1500 to 175°. A proximal portion of each armmay be generally rectangular and includes a proximal end having protrusionthat is, for example, an upward projecting triangular prism with triangular bases parallel with the sides of the respective arm. Protrusionis sized to fit notch or docking groovein transfer guideof a reagent cartridge (see). Cartridge lockmay be biased by a spring at each of pinswith shoulder closer to a surface of pedestal. In this configuration, at least a portion of protrusionextends above a base of the notches defining arm portionsof each dock. A downward force on protrusionwill cause protrusion to move downward and shoulder to move upward. Releasing such downward force will cause the opposite movement.

2152 2153 2152 125 120 120 115 125 125 125 An imager, such as a camera may be connected to pedestal or cartridge carrier plate. Representatively, an imager can be placed in one of slotsinstead of a dock and cartridge. Alternatively, an imager may be connected to an underside of carrier plate. An imager may be oriented to capture an image of a microscope slide (such as an image of an entire microscope slide, an image of an identifier (e.g., a label (e.g., a barcode)) on the microscope slide and/or an image of a sample on the microscope slide) when the microscope slide is removed from chamberof body(e.g., when dooris moved to an open position and slide bedmay be moved from a position inside chamberto a position outside chamber. Image capture may be controlled by a controller with instructions to, for example, capture an image of an identifier on a microscope slide prior to the microscope slide initially being moved into chamber, of a sample on the microscope slide following a dewaxing operation to locate the sample on the microscope slide (e.g., via detecting the sample (e.g., a stained sample)) to determine where to subsequently dispense a reagent (e.g., a primary reagent) and/or after a primary staining operation.

7 FIG. 11 FIG. 15 FIG. 218 206 205 202 209 217 2183 21762 2176 2154 2152 215 2176 2177 21554 2154 2176 2177 21554 21554 2179 217 2152 218 2152 21554 2177 2177 21552 2155 21555 2177 21772 21556 21552 2155 21552 2155 21555 21556 21772 2154 209 218 21762 d 2 Referring again to,and, a transfer of a reagent cartridge by arm assemblyfrom storage rackor from platforminside housingis described. Controllerincludes non-transitory, machine-readable instructions that include directing arm assembly to engage the reagent cartridge (e.g., reagent cartridge) with cartridge engagement headof arm assembly engaging protrusionson transfer guidesof the reagent cartridge. Such instructions also include instructions to transport the reagent cartridge to one of dockson pedestalof carouseland align transfer guidesandof the reagent cartridge with arm portionsof one of docks(align transfers guidesandrespectively above and below each arm portion). Once aligned, the instructions further include instructions to slide the reagent cartridge into arm portion(in a proximal to distal direction) so that snout or baseof reagent cartridgeis inward (e.g., faces a center of pedestal). Arm assemblyapplies a force in a direction of a center of pedestalsufficient to slide the reagent cartridge into arm portions. Transfer guide, having a thickness, t, greater than a thickness, t, of transfer guidewill contact a proximal portion of each armof cartridge lockand cause each arm to rotate about each pinand push the proximal portion of the arm downward. When that portion of transfer guidethat includes dock locking grooveis directly above protrusionof each armof cartridge lock, the bias of cartridge lock will cause each armof cartridge lockto rotate in an opposite direction about pinand cause protrusionto engage locking groove. At this point, the reagent cartridge is secured in dockand the instructions associated with controllerwill direct arm assemblyto release its engagement with each engaging protrusion.

2154 215 206 2190 206 204 2190 2190 2190 21901 21901 21903 21904 21903 21904 21903 21904 21905 21903 21904 21906 21903 21904 21902 21902 21905 21906 21907 21908 21907 21908 2154 6 FIG. 16 FIG. 18 FIG. Before a reagent cartridge is delivered to a dock (dock) on carouselfor a dispensing operation or returned to storage rackfrom a dock, the reagent cartridge may go to a service station.shows service stationadjacent storage rackmounted to a rear sidewall of reaction compartmentas viewed. Service stationprovides an area where a printhead of a reagent cartridge may be tested and cleaned prior to and/or after use in a dispensing operation to dispense reagent therefrom onto a microscope slide.shows a front side view of service station. Service stationin this example includes a rear wall. Connected to rear wallare pulley supportand pulley support. Each of pulley supportand pulley supportinclude an upper roller and a lower roller. Disposed on the upper roller of each of pulley supportand pulley supportis belt. Disposed on the lower roller of each of pulley supportand pulley supportis belt. Disposed between and connected to each of pully supportand pully supportis rail. Slidably connected to railand beltand beltis carriageand carriage. Each of carriageand carriagemay have a configuration to secure a reagent cartridge similar to dock(see).

16 FIG. 19 FIG. 21907 21908 2190 21907 21908 2170 2154 215 2170 21914 21907 21915 21908 1 1 1 1 1 1 2 2 In the example shown in, carriagehas a length, L, and a width, W, for a reagent cartridge of a first size, such as Lof 100 mm and Wof 60 mm and carriagehas a length, L, and a width, W, for a reagent cartridge of a second size, such as Lof 72 mm and Wof 60 mm. It is noted that service stationmay be equipped with only one carriage or, if multiple carriages are included, the carriages may accommodate reagent cartridges of the same or different length and width dimensions. A base or backside as viewed of each of carriageand carriageincludes electronic contacts or pins operable to mate with receptors (contacts) on a front side of a reagent cartridge similar to the interior surface of a back wall of each dockof carouselthat includes contacts that mate with contactson a reagent cartridge.shows contacts or pinsin carriageand contacts or pinsin carriage.

217 21907 21908 217 22794 21917 21907 21917 21907 21907 21908 15 FIG. In one example, a reagent cartridge (reagent cartridge) has length and width dimensions to fit snugly within carriageor carriage. As described above with respect to, a front of a reagent cartridge (reagent cartridge) includes electronic pin receptaclesto mate with electronic contacts or pinsin carriage. A front side of a reagent cartridge may also include two diagonally spaced alignment sockets or openings that align with alignment pinsin carriageto aide in the alignment of a reagent cartridge into carriageor carriage.

16 FIG. 21907 21908 21903 21904 21905 21906 21905 21906 21907 21908 21902 21907 21909 21912 21913 21909 21907 21908 11912 11913 109 21912 21913 shows each of carriageand carriageconnected to pulley supportand pulley supportthrough beltand belt. Beltand beltmay independently move or translate carriageand carriagelaterally along rail. Such movement allows each of carriageto bring a reagent container attached thereto to spittoonand to a wiping station (wiping stationor wiping station). Spittoonprovides a vessel for a reagent cartridge in carriageor carriageto dispense reagent. Each of wiping stationand wiping stationmay be a container (e.g., a rectangularly-shaped container containing a length of ribbon between rollers with the ribbon exposed at a top face or side of the container as viewed. The ribbon has a first side that is a cloth or similar absorbent material. A width of the ribbon may be at least as wide as a printhead of a reagent cartridge. The cloth or similar absorbent material provides a cleaning or wiping area for wiping a printhead (e.g., excess reagent on a printhead). After a wiping action by a printhead of a reagent cartridge on a portion of the ribbon, the ribbon may be advanced by instructions from controllerthat direct a movement of the rollers in wiping stationor.

209 21907 21908 2154 209 21907 21908 209 21909 21912 21913 Each carriage may be electrically connected and communicate with controller. Carriageand carriagecontain electronics to operate a reagent cartridge similar to electronics in dockto dispense reagent under the direction of non-transitory, machine-readable instructions associated with controller. When a reagent cartridge is connected to carriageor carriage, instructions from controllercan direct the dispensing of reagent from the reagent cartridge, for example, into spittoonand contact between the printhead of a reagent cartridge and a ribbon of wiping stationor wiping station.

209 21907 21908 21905 21906 21909 209 218 217 21907 209 21907 21909 209 21912 21913 209 218 2154 215 206 In a method of operation, instructions from controllermay direct a movement of one of carriageor carriageby beltsandover spittoon. At that time or a time before or after, instructions from controllermay direct arm assemblyto engage a reagent cartridge (e.g., reagent cartridge) and to install the reagent cartridge in the moved carriage (e.g., carriage). Further instructions from controllermay then include instructions to direct electronics in carriageto cause the reagent cartridge to dispense or spit an amount of reagent into spittoon(e.g., an amount sufficient to wet the printhead and ensure it is not clogged). Following a dispensing operation, instructions from controllermay direct that the reagent cartridge be brought to wiping stationor wiping stationto clean residual reagent on the printhead of the reagent cartridge through a wiping action by the printhead on a ribbon of the wiping station. After wiping, instructions from controllermay direct arm assemblyto engage the reagent container and deliver the reagent container to a dock (dock) on carouselfor a dispensing operation or to storage rack.

In the above discussion a reagent dispensing technique employing inkjet technology is described. A dispensing alternative includes a dispensing cartridge connected to a cartridge pump assembly that pumps a reagent from the dispensing cartridge onto a sample. Another dispensing alternative may include pipette transfer from a reagent container to a sample.

1 15 FIGS.- 204 112 209 130 120 155 112 115 125 120 120 115 115 209 2152 125 115 125 130 112 The following describes a representative operation of the sample processing system described with reference to. Initially, individual microscope slide(s) each containing at least one tissue sample will be brought to reaction compartmentby an operator or robot. Each microscope slide will be placed individually in a sample processor (sample processor). Non-transitory, machine-readable instructions from controllermay direct a door (door) of the bodyof a sample processor to open and then direct linear actuatorof a sample processorto move slide bedfrom a position inside the chamber (chamber) of bodyto a position outside the chamber. A microscope slide may then be placed with a tissue sample side facing upward (facing a top of body) or facing downward (facing slide bed). Once a slide is placed on slide bed, non-transitory, machine readable instructions from controllermay direct that an image of an identifier on the microscope slide be captured by an imager (e.g., an imager connected to pedestal or cartridge carrier plate) and further instructions may then direct the slide bed to be returned to inside chamber(direct linear actuator to move slide bedinside chamber) and direct the closing of doorof the respective reaction stations.

104 125 209 125 115 115 115 A microscope slide including a tissue sample brought to reaction compartmentmay be embedded with an embedding agent (e.g., paraffin) or may be processed to remove the embedding agent and adhere the tissue sample to the slide (i.e., pre-processed to remove the paraffin and adhere the tissue sample to the slide). Where a slide is brought to chamberhaving a tissue sample embedded with an embedding agent such as paraffin, non-transitory, machine-readable instructions from controllermay direct the system to perform an adherence and de-paraffinization (dewaxing) protocol on the embedded tissue sample. Representatively, instructions may direct that the slide with the embedded tissue sample be heated utilizing, for example, hot water introduced into a reservoir in chamberand/or a slide heater connected to slide bed(e.g., below slide bedor above slide bed) as part of a baking operation. The heat treatment should be sufficient to allow a sample on a slide to adhere or further adhere to a slide (a glass slide) and possibly to soften the embedding medium associated with a section on the slide. Representatively, the slide may be heated to a temperature on the order of 55° C. to 70° C.

125 115 209 159 158 209 209 201 204 190 120 209 190 115 209 209 115 140 115 1 FIG. 6 FIG. 5 FIG. 3 FIG. Following the heat treatment, instructions may direct that the heat be removed from chamber. If the reservoir below slide bedwas filled with hot water, the instructions from controllermay direct drain valve(see) to open and the hot water drained to a waste collector through conduit. If a slide heater(s) was(were) used, the instructions from controllermay direct that the slide heater(s) be turned off. Subsequent instructions from controllermay direct that the embedded tissue sample on the slide be exposed to a volume of a dewaxing solution such as xylene sufficient to coat the sample portion of slide. A dewaxing solution such as xylene may be stored in a container in storage compartmentbeneath reaction compartmentas a bulk reagent (see). The dewaxing solution container may be connected to a fluid connectoron a top of body(see) of the reaction compartment containing the embedded tissue sample on the slide. Instructions associated with controllermay direct that a dewaxing solution be transferred (e.g., pumped) from the dewaxing solution container to the respective fluid connectorand onto a surface of the slide in the reaction compartment if the tissue sample is facing upward or onto slide bedif the tissue sample is facing downward (toward the slide bed). Following dispensing of the dewaxing solution, the instructions associated with controllermay direct that the tissue sample soak in the dewaxing solution for a period of time (e.g., one minute to five minutes). Following the soak time, instructions associated with controllermay direct slide bedto be tilted by rotary motorto drain the dewax solution from the tissue sample and/or slide bed(see).

209 159 158 190 120 190 1 FIG. Following a period to remove the dewaxing solution and paraffin from the surface of the slide, further instructions associated with controllermay direct valve(see) to open and the dewaxing solution to be drained to a waste collector through conduit. In another example, a dewaxing protocol may involve the dispensing of several reagents sequentially. For example, a first reagent applied to a tissue sample on a slide may be xylene. After a xylene treatment and its subsequent removal, the dewaxing protocol may specify that the tissue sample be exposed to an alcohol (e.g., ethyl alcohol). In such instance, a container containing xylene will be connected to a first fluid connectoron a top of bodyand a container containing the alcohol will be connected to a second fluid connector.

209 190 120 209 115 158 159 Following a dewaxing process, instructions associated with controllermay direct that the tissue sample be rinsed with a volume of a washing solution, such as water or other aqueous wash solution. A container containing a wash solution may be connected to a fluid connector (fluid connector) on bodyto provide the washing solution to the tissue sample. The washing solution may also include an amount of stain such as eosin in the wash solution to stain a sample on a slide. Generally, following a dewaxing operation, an embedding material in the section is removed leaving the sample as a virtually colorless object on a slide. Adding an amount of a stain such as eosin in the wash solution may allow the presence and location of the sample on the slide to be detected. Following the washing process, instructions associated with controllermay direct slide bedto be rotated to remove the washing solution from a surface of the slide and direct the washing solution to be drained to a waste collector through conduitand valve.

209 130 120 155 112 115 125 120 209 2152 125 115 125 130 112 Following a washing process, non-transitory, machine-readable instructions from controllermay direct a door (door) of the bodyof a sample processor to open and then direct linear actuatorof a sample processorto move slide bedfrom a position inside the chamber (chamber) of bodyto a position outside the chamber. Additional instructions from controllermay direct that an image of a sample and possibly an identifier on the microscope slide be captured by an imager (e.g., an imager connected to pedestal or cartridge carrier plate) and further instructions may then direct the slide bed to be returned to inside chamber(direct linear actuator to move slide bedinside chamber) and direct the closing of doorof the respective reaction stations. Further instructions may direct that a position of the sample or a portion thereof on the microscope slide be located and stored for use in a staining operation.

209 201 204 190 120 209 209 125 125 172 120 125 170 115 125 209 156 125 156 125 157 154 125 157 125 157 1 FIG. Following a washing process and possible capture of an image of the sample and identifier, instructions associated with controllermay direct that the tissue sample be subjected to an antigen retrieval process to reverse the antigen masking effects of aldehyde fixation. A container containing an antigen retrieval solution, such as a tris- or citrate-based retrieval solution, may be stored in storage compartmentbeneath reaction compartmentas a bulk reagent and be connected to a fluid connector (fluid connector) on bodyvia a conduit to provide the antigen retrieval solution to the tissue sample. Instructions associated with controllermay direct that the antigen retrieval solution be provided to a surface of the tissue sample. Instructions associated with controllermay also direct that the antigen retrieval process be performed at an elevated temperature and possibly an elevated pressure. Representatively, instructions may direct that the slide with the tissue sample be heated utilizing a slide heater(s) in chamberto a temperature on the order of, for example, 100° C. to 130° C. Instructions may further direct that the reaction compartment be brought to an elevated pressure of, for example, 1.0 atmosphere (atm) (15 pounds per square inch (psi) to 1.7 atm (25 psi)) by, for example, introducing air or an inert gas into chambersuch as through fitting(e.g., a valve or valve and conduit) disposed in bodyto chamber(see) using compressor or pump. Utilizing an elevated pressure allows an antigen retrieval process to be expedited to, for example, a process time of five minutes compared to prior process times of 45 minutes or more under atmospheric conditions. In another example, an antigen retrieval process may be performed at an elevated humidity level, such as 70 percent to 100 percent relative humidity. As noted above, the humidity may be elevated by the inclusion of a fluid (e.g., water) below slide bedin chamberof a body. Before providing an antigen retrieval solution to a surface of a tissue sample, instructions from controllermay direct valvebe opened to allow a fluid into the chamber and a certain volume of fluid be introduced into chamberthrough valve. Steam produced in an external boiler may be supplied into chamber, such as through conduit. Instructions from controller may direct heat elementto heat the fluid. Alternatively, air or an inert gas (ambient or heated) may be bubbled through an external reservoir (ambient or heated) to produce humid air at a desired moisture level that could be supplied into chamber, such as through conduit. Further, an ultrasonic generator could produce water droplets (ambient or heated) that could be fed to chamber, such as through conduit.

209 209 125 158 159 115 158 159 209 115 158 159 Once an antigen retrieval process is completed, instructions associated with controllerinstructions associated with controllermay direct any fluid in chamberused to produce a desired humidity level be drained to a waste collector through conduitand valveand slide bedto be tilted to remove the antigen retrieval solution from a surface of the slide and drained to a waste collector through conduitand valve. Further instructions may then direct that the tissue sample be rinsed with a volume of a washing solution, such as water or a wash buffer such as TBS or phosphate-buffered saline containing a surfactant. Following washing, instructions associated with controllermay direct slide bedto be rotated to remove the wash solution from a surface of the microscope slide and drained to a waste collector through conduitand valve.

209 112 130 120 209 115 125 120 209 For a staining process, instructions associated with controllermay direct a motor associated with sample processorcontaining a microscope slide with a sample ready for staining to open a door (door) of body. Additional instructions from controllermay then direct slide bedto be moved outside a chamber (chamber) of body. If not done earlier, further instructions from controllermay direct that a location of the sample on the microscope slide or a portion thereof for staining be determined based on the captured image of the sample on the microscope slide following a washing operation.

209 206 2154 2152 215 209 2152 2157 2151 215 2143 215 209 Before or after a microscope slide is moved outside a chamber for a staining process, instructions associated with controllermay direct the retrieval of a reagent cartridge from storage rackand the loading or docking of the reagent cartridge at one of dockson pedestalof carousel. Further instructions associated with controllermay direct that the reagent cartridge loaded on pedestalbe positioned with a snout or base portion of the reagent cartridge is over the tissue sample on the raised slide. Such instructions include directing motorto rotate columnand accordingly pedestaland motorto move carouselin a longitudinal direction. Once positioned, instructions may direct the ejecting (e.g., printing) of reagent from the reagent cartridge onto the sample at the predetermined location of the sample or a portion thereof. Representatively, a drop-on-demand-type printhead, such as a thermal inkjet printhead, in the reagent cartridge may dispense a reagent, such as a detection agent or antibody, in droplets having a volume of 1 picoliter (pL) to 10 nanoliters (nL), or 1 pL to 5 nL, or 1 pL to 1 nL, or 1 pL to 500 pL, or 1 pL to 250 pL or 1 pL to 100 pL, or 1 pL to 50 pL. Representatively, an inkjet cartridge can deliver 15 microliters (μL) per square inch per pass or more (at least 15 μL) where a pass is a dispense (ejection) of reagent from the multiple nozzles in a printhead of an inkjet cartridge either while the reagent cartridge (carousel) and slide are stationary or where at least one of the reagent cartridge (carousel) and slide move unidirectionally to expand a dispense area on the slide. Representatively, controllerdirects a printhead of a reagent cartridge to dispense multiple drops (i.e., drops from multiple nozzles) to produce a higher volume of reagent per pass. Representative delivery amounts through a thermal inkjet printhead include 15 μL to 30 μL per square inch per pass, 15 μL to 25 μL per square inch per pass, and 15 μL to 20 μL per square inch per pass.

209 125 125 172 120 125 170 209 1 FIG. Instructions associated with controllermay also direct that a staining process be performed at an elevated temperature and possibly an elevated pressure. Representatively, instructions may direct that the slide with the tissue sample be heated utilizing a slide heater(s) in chamberto a desired temperature. Instructions may further direct that the reaction compartment be brought to an elevated pressure of, for example, 1.0 atmosphere (atm) (15 pounds per square inch (psi) to 2 atm (30 psi)) by, for example, introducing air or an inert gas into chambersuch as through fitting(e.g., a valve or valve and conduit) disposed in bodyto chamber(see) using compressor or pump. In another example, a staining process may be performed at an elevated humidity level, such as 70 percent to 100 percent relative humidity. As noted above, the humidity by techniques such as described above with respect to the antigen retrieval process may be directed by instructions from controllerfor a staining process.

209 115 125 130 120 209 209 209 115 125 158 159 209 209 130 120 112 115 125 Following a staining process, instructions associated with controllermay direct the movement of the reagent cartridge and carousel away from a position above the slide and direct a to return slide bedand the microscope slide to the chamber (chamber) and the closing of the door (door) of body. Additional instructions associated with controllermay direct that the sample on the microscope slide be extended an incubation period (to, for example, allow a primary antibody to bind to a targeted antigen). The incubation may be done in a humid environment. Following any incubation period, instructions associated with controllermay direct that the tissue sample be rinsed with a volume of a washing solution to remove any non-reacted/non-conjugated reagent. Following rinsing, instructions associated with controllermay direct slide bedto be rotated to a non-horizontal position in chamberto remove the wash solution from a surface of the slide. Additional instructions may then direct the wash solution to be drained to a waste collector through conduitand valve. Once all staining processes are finished for tissue sample on a microscope slide, instructions associated with controllermay direct the system to alert a user that the microscope slide is ready for removal. Additional instructions from controllermay then direct doorof bodyof sample processorto be opened and slide bedto be moved to a position where the microscope slide thereon is outside the chamber (chamber) to allow an operator or robot to retrieve the microscope slide.

112 The use of elevated pressure in a sealed sample processor such as sample processorwas evaluated for an antigen retrieval process versus a control at ambient pressure. Table 1 describes the samples, conditions and results. At 25 psi (1.7 atm), an antigen retrieval process was completed in five minutes or 10 minutes with satisfactory and comparable results to the control at ambient pressure completed in 30 minutes. The control conditions were ambient pressure, temperature of 80° C. to 90° C. and 80 percent to 100 percent humidity.

TABLE 1 Slide Reagent Conditions Time Result 1 High pH antigen retrieval on Pressure: 25 psi 5 minutes Satisfactory and tonsil tissue, stained with Temperature: 120- comparable to CK5/6 antibody 130° C. control results of Humidity: 80-100% no pressure and a time of 30 minutes 2 High pH antigen retrieval on Pressure: 25 psi 10 minutes  Satisfactory and tonsil tissue, stained with Temperature: 120- comparable to CK5/6 antibody 130° C. control results of Humidity: 80-100% no pressure and a time of 30 minutes 3 High pH antigen retrieval on Pressure: 25 psi 5 minutes Satisfactory and tonsil tissue, stained with Ki67 Temperature: 120- comparable to antibody 130° C. control results of Humidity: 80-100% no pressure and a time of 30 minutes 4 Citrate antigen retrieval on Pressure: 25 psi 5 minutes Satisfactory and brain tissue, stained EpCAM Temperature: 120- comparable to antibody 130° C. control results of Humidity: 80-100% no pressure and a time of 30 minutes 5 Citrate antigen retrieval on Pressure: 25 psi 5 minutes Satisfactory and brain tissue, stained Factor Temperature: 120- comparable to XIIIA antibody 130° C. control results of Humidity: 80-100% no pressure and a time of 30 minutes

112 The use of elevated pressure in a sealed sample processor such as sample processorwas evaluated for a reduction in antibody staining time versus a control at ambient pressure. Table 2 describes the samples, conditions and results. At 25 psi (1.7 atm), a process was completed in two minutes, another in five minutes and a third at 15 minutes with satisfactory and comparable results to the control at ambient pressure, ambient temperature and 80-100% humidity completed in 30 minutes.

TABLE 2 Antibody Incubation Slide Reagent/Tissue Conditions Time Conclusion 7 Citrate antigen retrieval on Pressure: 25 psi 2 minutes Satisfactory and brain tissue. Stained with Temperature: comparable to $100 antibody Ambient control results of Humidity: 80- no pressure and a 100% time of 30 minutes 8 Citrate antigen retrieval on Pressure: 25 psi 5 minutes Satisfactory and brain tissue. Stained with Temperature: comparable to $100 antibody Ambient control results of Humidity: 80- no pressure and a 100% time of 30 minutes 9 Citrate antigen retrieval on Pressure: 25 psi 15 minutes  Satisfactory and brain tissue. Stained with Temperature: comparable to S100 antibody Ambient control results of Humidity: 80- no pressure and a 100% time of 30 minutes

The specification includes the following aspects:

a body comprising an inner surface that defines a chamber including an opening in a side of the body and comprising a volume to accommodate a least one microscope slide therein; a door comprising a first position to cover the opening of the body and a second position to expose a portion of the chamber through the opening; a slide bed disposed in the chamber; and one of an internal humidity generator disposed in the chamber and an external humidity generator coupled to the chamber. 1. A sample processor comprising:

2. The sample processor of aspect 1, wherein the sample processor comprises an internal humidity generator and the internal humidity generator comprises a reservoir below the slide bed.

3. The sample processor of aspect 1 or aspect 2, further comprising a heat source.

4. The sample processor of any of aspects 1-3, wherein the heat source comprises a heater to heat a fluid in the reservoir.

5. The sample processor of aspect 3, wherein the heat source comprises a heater to heat the slide bed directly or indirectly.

6. The sample processor of any of aspects 1-5, further comprising a pressure source operable to increase a pressure in the chamber above ambient.

7. The sample processor of aspect 6, wherein the pressure source is operable to maintain a pressure in the chamber at at least 25 psi (1.7 atm).

8. The sample processor of aspect 6 or aspect 7, wherein the pressure source comprises a compressor coupled to and in fluid communication with the body operable to introduce air into the chamber.

9. The sample processor of aspect 1, wherein the sample processor comprises an external humidity generator.

10. The sample processor of aspect 9, further comprising at least one heat source.

11. The sample processor of aspect 9 or aspect 10, wherein the heat source comprises a heater to heat the slide bed directly or indirectly.

12. The sample processor of any of aspects 9-11, wherein the at least one heat source is operable to maintain a temperature in the chamber of at least 100° C.

13. The sample processor of any of aspects 1-12, wherein the body comprises an outer surface and an opposite inner surface, wherein the outer surface comprises a plurality of hose couplings coupled thereto, and the inner surface comprises a plurality of nozzles in fluid communication with respective ones of the plurality of hose couplings.

14. The sample processor of any of aspects 1-13, further comprising a nozzle in the chamber, the nozzle operable to be connected to a conduit outside the body and the nozzle operable to dispense a reagent in a spray or curtain flow toward the slide bed.

15. The sample processor of any of aspects 1-14, wherein the one of the internal humidity generators and the external humidity generator are operable to produce a humidity in the chamber greater than 60 percent.

16. A sample processing system comprising at least one of the sample processor of any of aspects 1-15 and further comprising at least one reagent outside the body of the at least one sample processor and coupled to a conduit that extends into the chamber of the at least one sample processor.

17. The sample processing system of aspect 16, wherein the at least one reagent may be heated to a temperature above ambient.

18. The sample processing system of aspect 16 or aspect 17, wherein the at least one sample processor is contained in a reaction compartment and the sample processing system comprises a refrigerated storage rack operable to store a number of reagent cartridges.

subjecting a sample on a microscope slide in a sealed chamber to a pressure greater than ambient and a humidity greater than 60 percent; and processing the sample. 19. A method comprising:

20. The method of aspect 19, wherein processing the sample comprises contacting the sample with a reagent.

21. The method of aspect 19 or aspect 20, wherein the reagent comprises a stain.

22. The method of any of aspects 19-21, wherein contacting the sample with a reagent comprises dispensing the reagent through a thermal inkjet process.

23. The method of aspect 22, wherein dispensing comprises dispensing the one or more reagents in an amount of at least 15 microliters (μL) per square inch per pass.

24. The method of any of aspects 19-23, wherein processing the sample comprises exposing antigenic sites in or on the sample.

25. The method of any of aspects 19-23, further comprising subjecting the sample to a temperature greater than ambient.

217 In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes can be made thereto without departing from the broader spirit and scope of the invention as set forth in the appended claims. For example, a reagent cartridge as disclosed herein (e.g. reagent cartridge) may contain solvent or water instead of a reagent and used for purposes other than, for example, staining a sample on a microscope slide. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.